Solid forms of a kynurenine-3-monooxygenase inhibitor

Patent metadata

Field	Value
Publication number	US-11173156-B2
Application number	US-202016898239-A
Country	US
Kind code	B2
Filing date	Jun 10, 2020
Priority date	Jun 11, 2019
Publication date	Nov 16, 2021
Grant date	Nov 16, 2021

Abstract

Forms of 6-(3-chloro-4-cyclopropoxyphenyl)pyrimidine-4-carboxylic acid (Compound I) were prepared and characterized in the solid state:Also provided are processes of manufacture and methods of using the forms of Compound I and salts or co-crystals thereof.

First claim

What is claimed is:

1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least about 85% w/w of a sodium salt of Compound I:

having a crystalline form characterized by an X-ray powder diffractogram comprising peaks at 3.36, 8.90, and 18.30°2θ±0.2°2θ, as determined on a diffractometer using Cu-Kα radiation (Compound I Sodium Form B).

2. The pharmaceutical composition of claim 1 , wherein the crystalline form is further characterized by one or more peaks at 10.15, 23.93, and 26.66°2θ±0.2°2θ.

3. The pharmaceutical composition of claim 1 , wherein the crystalline form is characterized by a differential scanning calorimetry curve comprising an endotherm with onset at about 184° C.

4. The pharmaceutical composition of claim 1 , comprising at least about 95% w/w of Compound I Sodium Form B.

5. The pharmaceutical composition of claim 1 , further comprising another therapeutic agent.

6. A method of treating a disease or condition mediated by Kynurenine 3-mono-oxygenase activity in a subject in need of such a treatment which method comprises administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 1 .

7. The method of claim 6 , wherein the disease or condition is:
spinocerebellar ataxia, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, trauma-induced neurodegeneration, high-pressure neurological syndrome, dystonia, olivopontocerebellar atrophy, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consequences of stroke, cerebral ischemia, an ischemic disorder, hypoxia, multi-infarct dementia, a consequence of cerebral trauma or damage, damage to the spinal cord, senile dementia, AIDS-dementia complex, AIDS-induced encephalopathy, other infection related encephalopathy, viral or bacterial meningitis, a general central nervous system (CNS) infection, poliomyelitis, Lyme disease (Borrelia burgdorferi infection), septic shock, malaria, cancer with cerebral localization, hepatic encephalopathy, systemic lupus, analgesia, an opiate withdrawal symptom, feeding behavior, psychiatric disorder, insomnia, depression, schizophrenia, severe deficit in working memory, severe deficit in long term memory storage, decreased cognition, severe deficit in attention, severe deficit in executive functioning, slowness in information processing, slowness in neural activity, a generalized anxiety disorder, panic anxiety, obsessive compulsive disorder, social phobia, performance anxiety, post-traumatic stress disorder, acute stress reaction, adjustment reaction, separation anxiety disorder, alcohol withdrawal anxiety, a disorder of the developing or aged brain, diabetes, Tourette's syndrome, Fragile X syndrome, autism spectrum disorder, bipolar disorder, unipolar depression, major depression, endogenous depression, involutional depression, reactive depression, psychotic depression, depression caused by an underlying medical condition, cyclothymic disorder, dysthymic disorder, mood disorder due to a general medical condition, substance-induced mood disorder, acute necrotizing pancreatitis, HIV-related disorder, AIDS, aseptic meningitis, brain disease, Gilles de la Tourette syndrome, Asperger syndrome, Rett syndrome, a pervasive developmental disorder, aging-related brain disease, developmental brain disease, burnout syndrome, carbon monoxide poisoning, cardiac arrest or insufficiency and hemorrhagic shock, cataract formation, aging of the eye, central nervous system disease, cerebrovascular disease, chronic fatigue syndrome, chronic stress, variants of Grand mal and petit mal epilepsy and Partial Complex Epilepsy, diabetes mellitus, dyskinesia, L-DOPA induced movement disorders, drug addiction, pain and cataract, drug dependence, drug withdrawal, feeding disorder, Guillain Barre-Syndrome, hepatic encephalopathy, an inflammatory disorder of the central or peripheral nervous system, inflammatory pain, neuropathic pain, migraine, allodynia, hyperalgesia pain, phantom pain, neuropathic pain related to diabetic neuropathy, multiple organ failure, near drowning, necrosis, neoplasms of the brain, nicotine addiction, alcoholism, cannabis addiction, benzodiazepine addiction, barbiturate addiction, morphine addiction, cocaine dependence, change in appetite, a sleep disorder, changes in sleep pattern, lack of energy, fatigue, low self-esteem, self-reproach inappropriate guilt, frequent thoughts of death or suicide, plans or attempts to commit suicide, feelings of hopelessness and worthlessness, psychomotor agitation or retardation, diminished capacity for thinking, concentration, or decisiveness, sepsis, spinal cord disease, systemic lupus erythematosus, traumatic damage to the brain and spinal cord, tremor syndrome and different movement disorder, poor balance, bradykinesia, rigidity, tremor, change in speech, loss of facial expression, micrographia, difficulty swallowing, drooling, dementia, confusion, fear, sexual dysfunction, language impairment, impairment in decision making, violent outbursts, aggression, hallucination, apathy, impairment in abstract thinking, cardiovascular disease, dyslipoproteinemia, dyslipidemias, cardiomegaly, atherosclerosis, myocardial infarction, congestive heart failure, coronary heart disease, hypertension, hypotension, benign hyperproliferative disease, malignant hyperproliferative disease, angiomas, endometriosis, obesity, Age-related Macular Degeneration, retinopathy, proliferation of endothelial cells and smooth muscle cells that cause restenosis as a consequence of stenting in the treatment of atherosclerosis, a hyperproliferative disorder involving fibroblasts, cardiac remodeling and failure associated with myocardial infarction, excessive wound healing, transplant rejection, graft versus host disease, chronic kidney disease, systemic inflammatory disorder, brain inflammatory disorder, or pneumococcal meningitis.

8. The method of claim 6 , wherein the disease or condition is acute necrotizing pancreatitis, a disorder of the developing or aged brain, psychiatric disorder, Alzheimer's disease, inflammation, cancer, schizophrenia, neurodegenerative disease, or transplant rejection.

9. The method of claim 6 , wherein the disease or condition is a neurodegenerative disease.

10. The method of claim 6 , wherein the disease or condition is Huntington's disease.

Assignees

• Chdi Foundation Inc

Inventors

• Toledo-Sherman Leticia M
• Dominguez Celia
• Khetarpal Vinod
• Houston Travis Lee
• Parent Stephan D
• Chen Jian-Xie
• Montgomery Charles H
• Banda Geetha

Classifications

• A61K31/505 Primary

  Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim · CPC title

• C07D239/28 Primary

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms · CPC title